Vascular Morphologic And Hemodynamic Study In Fibrotic Liver Using MRA And MR Blood Flow Analysis

Background and purposes:Liver cirrhosis is a major cause of morbidity and mortality for the patient with liver disease. Alcohol is the leading cause of liver cirrhosis in the western world. In China, cirrhosis is most commonly caused by hepatitis especially hepatitis B. In the end stage of the entity, due to the portal hypertension, it is associated with complicatied and debilitating clinical conditions. The more the disease progresses, the less blood flow to the liver, the worse the liver function will be. However, most patients with cirrhosis are asymptomatic due to the compensatory capacity of the liver. It is difficult to make an early diagnosis. Clinically quantitative analysis of liver function is still difficult. Imaging has advantage in diagnosis of cirrhosis. Well known imaging features of liver cirrhosis include nodularity, volume reduction, caudate lobe enlargement, splenomegaly, heterogeneous enhancement, decreased right to left lobe volume ratio, varices and ascites. We have noticed that on high resolution dynamic gadolinium enhanced MRI cirrhotic liver commonly have small hepatic veins even when other imaging features of cirrhosis are not present, but there was no quantitative analysis on it. There is a dual blood supply of the liver, i.e. hepatic artery and portal vein. Liver fibrosis induces hepatic hemodynamic changes. Increased resistance of hepatic sinus circulation causes reduced portal flow. Hepatic arterial blood flow changes so as to buffer the impact of portal flow alterations on total hepatic blood flow, thus tending to regulate total hepatic flow at a constant level. It seems that precession of liver fibrosis influent this mechanism. The purpose of the study is to investgate the morphologic change of the vessels due to the cirrhotic liver and to evaluate the relationship between the portal flow and hepatic arterial flow using MR Q-Flow analysis software.Material and methods:The medical ethics committee of our institution approval this study and written informed consent was obtained from all subjects prior to the exam.This study included two parts, and the interval time between pathologic diagnosis and MR Scaning and liver biopsy or surgical operation on all cases was less than 30 days.Firstly,64 patients (male:female 51:13) with hepatic fibrosis confirmed by biopsy or surgically and pathologicallyfrom September 2008 to December 2009, and 10 healthy volunteers (male:female 6:4).All 64 patients were divided into 4 groups based on the severity of the liver fibrosis namely S1, S2, S3 and S4. All subjects were examined after 6 hours fast, and then exams were repeated in every 3 minutes for 60 minutes postprandially. Portal flow was measured at the level of main portal vein 1-2cm to the bification. Portal vein caliber, length and thickness of spleen and wall thickness of the gallbladder were also measured as morphologic index and liver volume was calculated as well. Data processing was acquired on the workstation, Mean Velocity of Portal Vein(Vp), Mean Velocity of Hepatic Artery(Va), Mean Flux of Portal Vein (Fp), Mean Flux of Hepatic Artery (Fa), Peak Flux of Portal Vein (Fpp), Time of Fpp(Tpp), Flux of Hepatic Artery at Tpp(Fap), Rate of Increase of Portal Flux(Rpi),Rate of Descend of Portal Flux(Rpd), Rate of Arterial Compensation(Rac), Distribution of Liver Blood Inflow(Dlb), Peak Systolic Arterial Flow Velocity(Vas), End Diastolic Flow Velocity(Vad), Hepatic Pulse Index(PI) and Resistance Index(RI) were measured and calculated.Secondly,85 healthy liver donors (male:female 43:42) and 127 patients (male: female 91:36)with biopsy proven cirrhosis or fibrosis were selected retrospectively from the records of the Center for Liver Disease and Transplantation from January 2002 to March 2006 and from September 2008 to December 2009.All subjects underwent dynamic gadolinium-enhanced 3D MR at 1.5 T/3.0T including FSE T2WI, dynamic 3D spoiled gradient echo imaging with fat suppression. Portal veins, hepatic veins, inferior vena cava, renal vein, superior mesenteric vein and splenic vein diameters as well as caudate lobe dimensions/volume, right lobe width, right and left lobe volume, spleen volume, gallbladder wall and colon wall thickness, presence of splenorenal shunt and recanalized umbilical veins were determined independently by three radiologists. The data from each of the three reviewers were averaged to obtain the final measurement results.Results:1 Portal and hepatic arterial flow analysis1.1 The flow volume of portal vein/hepatic arteryMean values of portal flow volume in 5 groups were all raised postprandially. It was 87% in group S1,74% in group S2,57% in group S3,45% in group S4 and 90% in group C respectively. There was significantly difference between S3/S4 and C (p<0.01). When FpO>15.2ml/s, there was a sensitivity 85% and specificity 85% to diagnose liver fibrosis at stage3 or above, and the FpO cutoff flow rate of more than 16.2ml/s has a specificity of 98% and sensitivity of 42%. When Fpp<25.9ml/s, there was a sensitivity 85% and specificity 70% to diagnose liver fibrosis at stage3 or above, and the Fpp cutoff flow rate of lesss than 22.8ml/s has a specificity of 98% and sensitivity of 73%. There was a delay of peak time when the mean velocity values reached the top point along with severity of liver fibrosis, especially in group S4 (p<0.01). There was no difference for mean flow volume values of hepatic artery among all groups at fasting conditions (p>0.05). The hepatic arterial flow volume decreased postprandially, but without significant difference among all groups (p>0.05).1.2 Mean velocity of portal vein/hepatic arteryMean values of portal flow velocity in 5 groups were all raised postprandially, and it was 84% in group S1,98% in group S2,45% in group S3,24% in group S4 and 54% in group C respectively. There was significantly difference between S3/S4 and C (p<0.01). There was a delay of peak time when the mean velocity values reached the top point along with severity of liver fibrosis, especially in group S4 (p<0.01). There was a depressive trend of mean velocity values of hepatic artery in all groups postprandially. There was no significantly difference comparing hepatic arterial flow velocity values before and after a stantardized meal among fibrosis groups and control group (p>0.05).1.3 The cross section area of portal veinsAt the fasting state, main portal vein's cross section area in group S3 and S4 were larger than other groups(p<0.01). After meal, the portal veins'cross section areas were all increased in 5 groups, and the increased rates were 24% in S1,24% in S2, 17% in S3,14% in S4 and 29% in C respectively. There was significantly difference between S3/S4 and C (p<0.01).1.4 PI and RI of the hepatic arteryAfter a standardized meal, the hepatic arteries' PI and RI values were all increased in 5 groups, and the increase rates of PI were 350% in S1,358% in S2, 347% in S3,146% in S4 and 370% in C respectively. There was significantly difference between S4 and C (p<0.01). The increase rates of RI were 54% in S1,49% in S2,20% in S3,18% in S4 and 58% in C respectively. There was significantly difference between S3/S4 and C (p<0.01).2. Changes of the major vessels of the liverHepatic veins in 4 fibrotic liver groups were 9.8mm,7.2mm,9.2 mm in S1, 9.2mm,7.5mm,9 mm in S2 group,8mm,7mm,6 mm in S3 group and 4.9mm,4.5mm,5.0mm in S4 group for right, middle and left compared to 9.9,7.6 and 8.9 mm in C group. Hepatic veins were significantly smaller in S4 compared to group C(p<< 0.001) and were negatively correlated with cirrhosis (r=-0.7,-0.6 and -0.6 respectively, p< 0.001). A right hepatic vein diameter< 5mm diagnosed cirrhosis with sensitivity= 57% but specificity=99%. Right portal veins were smaller in cirrhotic patients (group S4) measuring 6.4 mm (anterior) and 6.2 (posterior) mm, compared to 8.4 and 7.6 mm (p<< 0.001) in group C in spite of higher portal pressure in patients with cirrhosis. Left portal vein was only smaller in cirrhotic patients without recanalized umbilical vein. Mean caliber of proper hepatic artery were S1 (4.0±.1mm), S2(4.1±1.3mm), S3(4.2±1.5mm)and S4(4.1±1.5mm) respectively, and there was no significant difference compared to C(4.0±1.1mm) (p>0.05).Conclusions:1. Hepatic veins'diameter reduction inversely correlates with cirrhosis and may help diagnose cirrhosis when other imaging features of cirrhosis are absent. A right hepatic vein less than 5 mm in diameter on cross-sectional imaging should raise a high suspicion for cirrhosis when there are no large accessory right hepatic veins. There was no obvious change on hepatic arterial caliber when liver fibrosis happened.2. Hepatic arterial buffer response was proved. If liver fibrosis was more severe than fibrosis of stage 3, this buffer response couldnot meet the requirement of liver function.3. Portal blood flow velocity and volume are significantly influenced increasingly by food no matter with or without liver fibrosis, and reached the peak values around 30 minutes after meal. Hepatic arterial flow which was not correlated with meal decreased along with portal flow increasing.4. When the severity of liver fibrosis is more than stage 3, the cross section area of main portal vein increases compensatively in order to increase the portal blood flow, which was the self-regulatory response of portal vein.The followings may suggest the block of portal flow as well as portal hypertension:delay when portal flow velocity and volume reach to the peak value postprandially, postprandial cross section area of portal vein increases unconspicuously5. Fasting hepatic artery's PI and RI of fibrotic liver with stage 3-4 are significantly higher than normal liver and fibrotic liver with stage 1-2, but increase rate of PI and RI for stage 3-4 fibrotic liver postprandial comparing to fasting are significantly lower than other stages and normal liver. It is suggested that hepatic artery's buffer ablility is weaker in severe fibrotic liver than in the normal.6. When the severity of liver fibrosis is more than stage 3, invalid blood flow through the fibrotic liver increases and the function disorder of severe fibrotic liver will occur. The FpO cutoff flow rate of more than 16.2ml/s and the Fpp cutoff flow rate of lesss than 22.8ml/s have a specificity of 98% for liver fibrosis diagnosis of stage3-4.7. Liver vascular morphology and hemodynamic are related to pathologic change of fibrosis. MR techniques may help to dignose liver fibrosis and portal hypertension in early stage.